PMID- 11641240
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20151119
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 15
IP  - 12
DP  - 2001 Oct
TI  - Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune 
      disease, by blockade of IL-18.
PG  - 2140-8
AB  - Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an 
      important role in interferon gamma (IFN-gamma) production and IL-12-driven Th1 
      phenotype polarization. Increased expression of IL-18 has been observed in 
      several autoimmune diseases. In this study we have analyzed the role of IL-18 in 
      an antibody-mediated autoimmune disease and elucidated the mechanisms involved in 
      disease suppression mediated by blockade of IL-18, using experimental autoimmune 
      myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, 
      antibody-mediated autoimmune disease in which the nicotinic acetylcholine 
      receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both 
      implicated in EAMG development. We show that treatment by anti-IL-18 during 
      ongoing EAMG suppresses disease progression. The protective effect can be 
      adoptively transferred to naive recipients and is mediated by increased levels of 
      the immunosuppressive Th3-type cytokine TGF-beta and decreased AChR-specific 
      Th1-type cellular responses. Suppression of EAMG is accompanied by 
      down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a 
      key negative immunomodulator. Our results suggest that IL-18 blockade may 
      potentially be applied for immunointervention in myasthenia gravis.
FAU - Im, S H
AU  - Im SH
AD  - Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, 
      Israel.
FAU - Barchan, D
AU  - Barchan D
FAU - Maiti, P K
AU  - Maiti PK
FAU - Raveh, L
AU  - Raveh L
FAU - Souroujon, M C
AU  - Souroujon MC
FAU - Fuchs, S
AU  - Fuchs S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Cytokines)
RN  - 0 (Immunoconjugates)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-18)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Transforming Growth Factor beta)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 7D0YB67S97 (Abatacept)
SB  - IM
MH  - Abatacept
MH  - Animals
MH  - Antibodies/*therapeutic use
MH  - Antigens, CD
MH  - Antigens, Differentiation/biosynthesis
MH  - B-Lymphocytes/immunology
MH  - CD40 Ligand/metabolism
MH  - CTLA-4 Antigen
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Disease Progression
MH  - Female
MH  - Hypersensitivity, Delayed/therapy
MH  - *Immunoconjugates
MH  - Immunoglobulin G/biosynthesis
MH  - Interleukin-18/*antagonists & inhibitors/immunology
MH  - Kinetics
MH  - Lymphocyte Activation
MH  - Myasthenia Gravis, Autoimmune, Experimental/immunology/*therapy
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Receptors, Nicotinic/immunology
MH  - T-Lymphocytes/immunology
MH  - Th1 Cells/immunology
MH  - Transforming Growth Factor beta/biosynthesis
EDAT- 2001/10/20 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/20 10:00
PHST- 2001/10/20 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/20 10:00 [entrez]
AID - 15/12/2140 [pii]
AID - 10.1096/fj.01-0072com [doi]
PST - ppublish
SO  - FASEB J. 2001 Oct;15(12):2140-8. doi: 10.1096/fj.01-0072com.